Modified T Cells Expressing Cytokines for Solid Tumor Therapy
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Solution Overview
Problem
Current immunotherapy, such as CAR T cell therapy, is not sufficiently effective for treating solid tumors, and there is a need to enhance T cell response to improve cancer treatment outcomes.
Innovation Solution
Development of modified T cells expressing and secreting therapeutic agents like IFN-γ, IL-2, IL-6, IL-7, IL-15, and IL-17, which are encoded by specific nucleic acids, to enhance T cell response and improve cancer treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T cell therapy is used to treat solid tumors, then cancer treatment is provided, but T cell response is insufficient leading to poor treatment outcomes
Solution Approach 1:
The patent combines CAR T cell therapy with secretion of therapeutic cytokines (IL-2, IL-15, IL-21) by modifying T cells to express both the chimeric antigen receptor and cytokine genes. This merging of targeting capability and immunomodulatory function enhances T cell response and treatment effectiveness against solid tumors
Solution Approach 2:
The patent introduces cytokines as intermediary substances that mediate between the CAR T cells and the tumor microenvironment. These cytokines act as messengers to enhance T cell activation, proliferation, and persistence, thereby improving the overall therapeutic response
2Reliability
If therapeutic agents are secreted to enhance T cell response, then treatment efficacy is improved, but cytokine release syndrome may occur
Solution Approach 1:
The patent modifies the parameters of cytokine secretion by using regulated expression systems (inducible promoters, antigen-dependent expression) to control when and how much cytokine is produced. This allows optimization of therapeutic effect while minimizing the risk of excessive cytokine release that could cause syndrome
Solution Approach 2:
The patent implements feedback control mechanisms where cytokine expression is linked to antigen recognition events. The T cells sense the presence of target antigens and adjust cytokine secretion accordingly, providing a self-regulating system that reduces the risk of uncontrolled cytokine release
Data Source
AI summary
Compositions and methods for enhancing T cell response which increases the efficacy of CAR T cell therapy for treating cancer are described. Embodiments include a modified cell comprising an isolated nucleic acid comprising a first nucleic acid and a second nucleic acid, the first nucleic acid encoding a chimeric antigen receptor (CAR), the second nucleic acid encoding a therapeutic agent comprising at least one of IFN-γ, IL-2, IL-6, IL-7, IL-15, IL-17, and IL-23. The modified cell expresses and secretes the therapeutic agent.